Written by Kevin Liu
Spoon Feed
For the treatment of obesity in non-diabetic adults, tirzepatide was superior to semaglutide in both body weight reduction (20.2% tirzepatide vs 13.7% semaglutide) and waist circumference.
In a battle of heavyweight GLP-1s, tirzepatide loses more weight
Glucagon-like peptide-1 receptor agonist (GLP-1) drugs currently account for 29 billion dollars of the total US healthcare marketplace. All of them provide significant weight loss, none of them are cheap, so which do we recommend for non-diabetic patients? Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 agonist, appears to provide the greatest and most significant weight loss in the drug class. This randomized, controlled, open-label study, funded by Eli Lilly (owners of tirzepatide), validates network meta-analyses that have suggested tirzeptide’s superior efficacy over other GLP-1 receptor agonists. In a study that lasted 72 weeks and involved 751 non-diabetic obese participants across 33 sites in the United States, tirzepatide demonstrated statistically significant weight loss: −20.2% (95%CI −21.4 to −19.1) vs −13.7% (95%CI −14.9 to −12.6, P<0.001) and waist circumference reduction: −18.4 cm (95%CI −19.6 to −17.2) and −13.0 cm (95%CI −14.3 to −11.7, P<0.001).
Serious adverse effects were more common in the tirzepatide group (4.8%) compared to the semaglutide group (3.5%).
How does this change my practice?
As a hospitalist, my main exposure to GLP-1 antagonists comes from admissions for drug-related complications. I am concerned that tirzepatide had more serious adverse events, which was not further characterized in the article or supplement. While I think this study and the studies linked above would support the use of tirzepatide over other GLP-1 receptor agonist first due to its greater efficacy and more clinical indications, I am curious if this might lead to a higher rate of urgent care visits or hospital admissions.
Source
Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025 May 11. doi: 10.1056/NEJMoa2416394. Epub ahead of print. PMID: 40353578
